131 results on '"Xinyi Cheng"'
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2. Berberine alleviates high-energy and low-protein diet-induced fatty liver hemorrhagic syndrome in laying hens: insights from microbiome and metabolomics
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Xinyi Cheng, Yang Hu, Jun Kuang, Xiaoquan Guo, Huabin Cao, Huansheng Wu, Guoliang Hu, and Yu Zhuang
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fatty liver hemorrhagic syndrome ,Berberine ,gut microbiota ,metabolites ,fecal microbiota transplantation ,Animal culture ,SF1-1100 - Abstract
ABSTRACT: Berberine (BBR), a well-known quaternary ammonium alkaloid, is recognized for its ability to prevent and alleviate metabolic disorders because of its anti-oxidative and anti-inflammatory properties. However, the underlying mechanisms of BBR to mitigate fatty liver hemorrhagic syndrome (FLHS) through the modulation of gut microbiota and their metabolism remained unclear. The results revealed that BBR ameliorates lipid metabolism disorder in high-energy and low-protein (HELP) diet-induced FLHS laying hens, as evidenced by improved liver function and lipid deposition of the liver, reduced blood lipids, and the expression of liver lipid synthesis-related factors. Moreover, BBR alleviated HELP diet-induced barrier dysfunction, increased microbial population, and dysregulated lipid metabolism in the ileum. BBR reshaped the HELP-perturbed gut microbiota, particularly declining the abundance of Desulfovibrio_piger and elevating the abundance of Bacteroides_salanitronis_DSM_18170. Meanwhile, metabolomic profiling analysis revealed that BBR reshaped microbial metabolism and function, particularly by reducing the levels of hydrocinnamic acid, dehydroanonaine, and leucinic acid. Furthermore, fecal microbiota transplantation (FMT) experiments revealed that BBR-enriched gut microbiota alleviated hepatic lipid deposition and intestinal inflammation compared with those chicks that received a gut microbiota by HELP. Collectively, our study provided evidence that BBR effectively alleviated FLHS induced by HELP by reshaping the microbial and metabolic homeostasis within the liver-gut axis.
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- 2024
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3. Glucagon-like peptide-1 receptor agonists: new strategies and therapeutic targets to treat atherosclerotic cardiovascular disease
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Tianyu Wang, Juncan Ding, Xinyi Cheng, Qiang Yang, and Pengfei Hu
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glucagon-like peptide-1 receptor agonists ,atherosclerosis ,cardiovascular outcome trials ,inflammation ,mitochondrial dysfunction ,Therapeutics. Pharmacology ,RM1-950 - Abstract
Atherosclerotic cardiovascular disease (ASCVD) is a leading cause of cardiovascular mortality and is increasingly prevalent in our population. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) can safely and effectively lower glucose levels while concurrently managing the full spectrum of ASCVD risk factors and improving patients’ long-term prognosis. Several cardiovascular outcome trials (CVOTs) have been carried out to further investigate the cardiovascular benefits of GLP-1RAs. Analyzing data from CVOTs can provide insights into the pathophysiologic mechanisms by which GLP-1RAs are linked to ASCVD and define the use of GLP-1RAs in clinical practice. Here, we discussed various mechanisms hypothesized in previous animal and preclinical human studies, including blockade of the production of adhesion molecules and inflammatory factors, induction of endothelial cells’ synthesis of nitric oxide, protection of mitochondrial function and restriction of oxidative stress, suppression of NOD-like receptor thermal protein domain associated protein three inflammasome, reduction of foam cell formation and macrophage inflammation, and amelioration of vascular smooth muscle cell dysfunction, to help explain the cardiovascular benefits of GLP-1RAs in CVOTs. This paper provides an overview of the clinical research, molecular processes, and possible therapeutic applications of GLP-1RAs in ASCVD, while also addressing current limitations in the literature and suggesting future research directions.
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- 2024
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4. Sodium butyrate alleviates free fatty acid-induced steatosis in primary chicken hepatocytes via the AMPK/PPARα pathway
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Jiayi Ding, Jiuyue Liu, Jinyan Chen, Xinyi Cheng, Huabin Cao, Xiaoquan Guo, Guoliang Hu, and Yu Zhuang
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sodium butyrate ,free fatty acid ,primary chicken hepatocyte ,steatosis ,Animal culture ,SF1-1100 - Abstract
ABSTRACT: Fatty liver hemorrhagic syndrome (FLHS) is a prevalent metabolic disorder observed in egg-laying hens, characterized by fatty deposits and cellular steatosis in the liver. Our preliminary investigations have revealed a marked decrease in the concentration of butyric acid in the FLHS strain of laying hens. It has been established that sodium butyrate (NaB) protects against metabolic disorders. However, the underlying mechanism by which butyrate modulates hepato-lipid metabolism to a great extent remains unexplored. In this study, we constructed an isolated in vitro model of chicken primary hepatocytes to induce hepatic steatosis by free fatty acids (FFA). Our results demonstrate that treatment with NaB effectively mitigated FFA-induced hepatic steatosis in chicken hepatocytes by inhibiting lipid accumulation, downregulating the mRNA expression of lipo-synthesis-related genes (sterol regulatory element binding transcription factor 1 (SREBF1), acetyl-CoA carboxylase 1(ACC1), fatty acid synthase (FASN), stearoyl-CoA desaturase 1 (SCD1), liver X receptor α (LXRα), 3-hydroxy-3-methylglutaryl-CoA reductase (HMGR)) (P < 0.05), and upregulating the mRNA and protein expression of AMP-activated protein kinase α1 (AMPKα1), peroxisome proliferator-activated receptor α (PPARα), and carnitine palmitoyl-transferase 1A (CPT1A) (P < 0.05). Moreover, AMPK and PPARα inhibitors (Compound C (Comp C) and GW6471, respectively) reversed the protective effects of NaB against FFA-induced hepatic steatosis by blocking the AMPK/PPARα pathway, leading to lipid droplet accumulation and triglyceride (TG) contents in chicken primary hepatocytes. With these findings, NaB can alleviate hepatocyte lipoatrophy injury by activating the AMPK/PPARα pathway, promoting fatty acid oxidation, and reducing lipid synthesis in chicken hepatocytes, potentially being able to provide new ideas for the treatment of FLHS.
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- 2024
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5. An empirical analysis of the impact of the coupling coordination degree of the water-energy-food nexus on food security in China
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Xinyi Cheng, Lan Fang, Jun Li, and Heng Wang
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Water-energy-food(WEF) nexus ,Coupling coordination degree ,Food security ,China ,Environmental sciences ,GE1-350 ,Environmental protection ,TD169-171.8 - Abstract
Food security has been challenging in many countries due to climate change, population growth, water scarcity, and bio-energy development. This work quantifies the impact of water-energy-food (WEF) nexus coupling coordination on food security in China through a multidimensional approach to promote food security and resource sustainability. We first quantify the coupling coordination degree of the WEF nexus using the entropy weight TOPSIS (Technique for Order Preference by Similarity to Ideal Solution) method. And then Ordinary Least Squares Multiple Linear Regression model is employed to explore the impact of the WEF nexus coupling coordination degree on food security. The findings show that an improvement of 1% in the coupling coordination degree of the WEF increases the total grain yield, per capita grain yield, grain yield per unit by 2.69%, 1.12% and 2.77%, respectively. It is also found that improvement of WEF coupling coordination is conducive to enhancing food self-sufficiency rate and stabilizing food price. And the increment in grain yield is achieved by increasing the effective irrigated area and agricultural machinery inputs. Furthermore, the heterogeneity analysis reveals that the effect of the WEF nexus on the total grain yield and per capita yield is more significant in the central region, and the improvement of grain yield per unit is more effective in the west. Meanwhile, the interaction term analysis demonstrates that cropping structure, agricultural subsidies, and water-saving technologies all strengthen the positive contribution of the WEF nexus to food security.
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- 2024
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6. Antimicrobial Properties of Carboxymethyl Cellulose/Starch/N’N Methylenebisacrylamide Membranes Endowed by Ultrasound and Their Potential Application in Antimicrobial Packaging
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Youliang Cheng, Xinyi Cheng, Changqing Fang, Jing Chen, Xin Zhang, Changxue Cao, and Jinpeng Wang
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sonochemistry ,antibacterial properties ,carboxymethyl cellulose ,Organic chemistry ,QD241-441 - Abstract
Cellulose is used widely in antimicrobial packaging due to its abundance in nature, biodegradability, renewability, non-toxicity, and low cost. However, how efficiently and rapidly it imparts high antimicrobial activity to cellulose-based packaging materials remains a challenge. In this work, Ag NPs were deposited on the surface of carboxymethyl cellulose/starch/N’N Methylenebisacrylamide film using ultrasonic radiation. Morphology and structure analysis of as-prepared films were conducted, and the antibacterial effects under different ultrasonic times and reductant contents were investigated. These results showed that Ag NPs were distributed uniformly on the film surface under an ultrasonic time of 45 min. The size of Ag NPs changes as the reducing agent content decreases. The composite film demonstrated a slightly better antibacterial effect against E. coli than against S. aureus. Therefore, this work can provide valuable insights for the research on antimicrobial packaging.
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- 2024
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7. Unveiling Gene Expression Dynamics during Early Embryogenesis in Cynoglossus semilaevis: A Transcriptomic Perspective
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Xinyi Cheng, Wei Jiang, Qian Wang, Kaiqiang Liu, Wei Dai, Yuyan Liu, Changwei Shao, and Qiye Li
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Cynoglossus semilaevis ,Cynoglossidae ,gametes ,early embryonic development ,transcriptomics ,Science - Abstract
Commencing with sperm–egg fusion, the early stages of metazoan development include the cleavage and formation of blastula and gastrula. These early embryonic events play a crucial role in ontogeny and are accompanied by a dramatic remodeling of the gene network, particularly encompassing the maternal-to-zygotic transition. Nonetheless, the gene expression dynamics governing early embryogenesis remain unclear in most metazoan lineages. We conducted transcriptomic profiling on two types of gametes (oocytes and sperms) and early embryos (ranging from the four-cell to the gastrula stage) of an economically valuable flatfish–the Chinese tongue sole Cynoglossus semilaevis (Pleuronectiformes: Cynoglossidae). Comparative transcriptome analysis revealed that large-scale zygotic genome activation (ZGA) occurs in the blastula stage, aligning with previous findings in zebrafish. Through the comparison of the most abundant transcripts identified in each sample and the functional analysis of co-expression modules, we unveiled distinct functional enrichments across different gametes/developmental stages: actin- and immune-related functions in sperms; mitosis, transcription inhibition, and mitochondrial function in oocytes and in pre-ZGA embryos (four- to 1000-cell stage); and organ development in post-ZGA embryos (blastula and gastrula). These results provide insights into the intricate transcriptional regulation of early embryonic development in Cynoglossidae fish and expand our knowledge of developmental constraints in vertebrates.
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- 2024
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8. Low complexity domains of the nucleocapsid protein of SARS-CoV-2 form amyloid fibrils
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Einav Tayeb-Fligelman, Jeannette T. Bowler, Christen E. Tai, Michael R. Sawaya, Yi Xiao Jiang, Gustavo Garcia, Sarah L. Griner, Xinyi Cheng, Lukasz Salwinski, Liisa Lutter, Paul M. Seidler, Jiahui Lu, Gregory M. Rosenberg, Ke Hou, Romany Abskharon, Hope Pan, Chih-Te Zee, David R. Boyer, Yan Li, Daniel H. Anderson, Kevin A. Murray, Genesis Falcon, Duilio Cascio, Lorena Saelices, Robert Damoiseaux, Vaithilingaraja Arumugaswami, Feng Guo, and David S. Eisenberg
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Science - Abstract
Abstract The self-assembly of the Nucleocapsid protein (NCAP) of SARS-CoV-2 is crucial for its function. Computational analysis of the amino acid sequence of NCAP reveals low-complexity domains (LCDs) akin to LCDs in other proteins known to self-assemble as phase separation droplets and amyloid fibrils. Previous reports have described NCAP’s propensity to phase-separate. Here we show that the central LCD of NCAP is capable of both, phase separation and amyloid formation. Within this central LCD we identified three adhesive segments and determined the atomic structure of the fibrils formed by each. Those structures guided the design of G12, a peptide that interferes with the self-assembly of NCAP and demonstrates antiviral activity in SARS-CoV-2 infected cells. Our work, therefore, demonstrates the amyloid form of the central LCD of NCAP and suggests that amyloidogenic segments of NCAP could be targeted for drug development.
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- 2023
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9. Advances in macrocyclic chelators for positron emission tomography imaging
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Mengting Li, Sheng Wang, Qunshou Kong, Xinyi Cheng, Huanhuan Yan, Yao Xing, Xiaoli Lan, and Dawei Jiang
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bifunctional chelator ,macrocyclic chelators ,PET ,radiometals ,radiopharmaceuticals ,Biotechnology ,TP248.13-248.65 ,Medical technology ,R855-855.5 - Abstract
Abstract In recent years, radiometals have been successfully applied to medicine because of their breadth of decay properties and increased production and availability. Bifunctional chelators play a key role in radiometal‐based radiopharmaceuticals, affecting the labeling, targeting, and pharmacokinetics of bioconjugations and ensuring the stable complexation of the metal in vivo. The capacity of macrocycles to form complexes with extremely high thermodynamics, kinetics, and stability compared to acyclic chelators continues to pique the curiosity of pharmacists and biochemists among all prospective chelators utilized for the radiometal chelation. As new imaging modalities and therapeutic targets develop, the discovery of novel ligand structures with suitable chemical and biological features encourages the modification of chelators with charge and chemical properties. Herein, we present a comprehensive review of developments of macrocyclic chelators for PET radiopharmaceuticals, including innovative chelating agents with new structures and known chelating agent modifications, and their physical‐chemical properties, as well as their biological characteristics and applications in vivo.
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- 2023
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10. Integrated Small Animal PET/CT/RT with Onboard PET/CT Image Guidance for Preclinical Radiation Oncology Research
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Xinyi Cheng, Dongxu Yang, Debabrata Saha, Xiankai Sun, and Yiping Shao
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onboard PET/CT image ,PET/CT/RT ,preclinical radiotherapy research ,small animal PET ,Computer applications to medicine. Medical informatics ,R858-859.7 - Abstract
We have integrated a compact and lightweight PET with an existing CT image-guided small animal irradiator to enable practical onboard PET/CT image-guided preclinical radiation therapy (RT) research. The PET with a stationary and full-ring detectors has ~1.1 mm uniform spatial resolution over its imaging field-of-view of 8.0 cm diameter and 3.5 cm axial length and was mechanically installed inside the irradiator in a tandem configuration with CT and radiation unit. A common animal bed was used for acquiring sequential dual functional and anatomical images with independent PET and CT control and acquisition systems. The reconstructed dual images were co-registered based on standard multi-modality image calibration and registration processes. Phantom studies were conducted to evaluate the integrated system and dual imaging performance. The measured mean PET/CT image registration error was ~0.3 mm. With one-bed and three-bed acquisitions, initial tumor focused and whole-body [18F]FDG animal images were acquired to test the capability of onboard PET/CT image guidance for preclinical RT research. Overall, the results have shown that integrated PET/CT/RT can provide advantageous and practical onboard PET/CT image to significantly enhance the accuracy of tumor delineation and radiation targeting that should enhance the existing and enable new and potentially breakthrough preclinical RT research and applications.
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- 2023
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11. Enzymatic Synthesis of Structured Lipids Enriched with Medium- and Long-Chain Triacylglycerols via Pickering Emulsion-Assisted Interfacial Catalysis: A Preliminary Exploration
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Zhe Dong, Ziheng Cui, Jun Jin, Xinyi Cheng, Gangcheng Wu, Xingguo Wang, and Qingzhe Jin
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medium- and long-chain triacylglycerol ,pickering emulsion interfacial catalysis ,enzymatic trans-esterification ,tunnel analysis ,molecular dynamics simulation ,Organic chemistry ,QD241-441 - Abstract
Medium- and long-chain triacylglycerol (MLCT), as a novel functional lipid, is valuable due to its special nutritional properties. Its low content in natural resources and inefficient synthesis during preparation have limited its practical applications. In this study, we developed an effective Pickering emulsion interfacial catalysis system (PE system) for the enzymatic synthesis of MLCT by trans-esterification. Lipase NS 40086 served simultaneously as a catalyst and a solid emulsifier to stabilize the Pickering emulsion. Benefitting from the sufficient oil–water interface, the obtained PE system exhibited outstanding catalytic efficiency, achieving 77.5% of MLCT content within 30 min, 26% higher than that of a water-free system. The Km value (0.259 mM) and activation energy (14.45 kJ mol−1) were 6.8-fold and 1.6-fold lower than those of the water-free system, respectively. The kinetic parameters as well as the molecular dynamics simulation and the tunnel analysis implied that the oil–water interface enhanced the binding between substrate and lipase and thus boosted catalytic efficiency. The conformational changes in the lipase were further explored by FT-IR. This method could give a novel strategy for enhancing lipase activity and the design of efficient catalytic systems to produce added-value lipids. This work will open a new methodology for the enzymatic synthesis of structured lipids.
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- 2024
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12. Sodium Butyrate Alleviates Free Fatty Acid-Induced Steatosis in Primary Chicken Hepatocytes via Regulating the ROS/GPX4/Ferroptosis Pathway
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Xinyi Cheng, Yang Hu, Xiaoqing Yu, Jinyan Chen, Xiaoquan Guo, Huabin Cao, Guoliang Hu, and Yu Zhuang
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fatty liver hemorrhagic syndrome ,sodium butyrate ,ferroptosis ,steatosis ,ferrostatin-1 ,RSL3 ,Therapeutics. Pharmacology ,RM1-950 - Abstract
Fatty liver hemorrhagic syndrome (FLHS) in laying hens is a nutritional metabolic disease commonly observed in high-yielding laying hens. Sodium butyrate (NaB) and ferroptosis were reported to contribute to the pathogenesis of fatty liver-related diseases. However, the underlying mechanism of NaB in FLHS and whether it mediates ferroptosis remains unclear. A chicken primary hepatocyte induced by free fatty acids (FFAs, keeping the ratio of sodium oleate and sodium palmitate concentrations at 2:1) was established, which received treatments with NaB, the ferroptosis inducer RAS-selective lethal 3 (RSL3), and the inhibitor ferrostatin-1 (Fer-1). As a result, NaB increased biochemical and lipid metabolism indices, and the antioxidant level, while inhibiting intracellular ROS accumulation and the activation of the ferroptosis signaling pathway, as evidenced by a reduction in intracellular iron concentration, upregulated GPX4 and xCT expression, and inhibited NCOA4 and ACSL4 expression. Furthermore, treatment with Fer-1 reinforced the protective effects of NaB, while RSL3 reversed it by blocking the ROS/GPX4/ferroptosis pathway, leading to the accumulation of lipid droplets and oxidative stress. Collectively, our findings demonstrated that NaB protects hepatocytes by regulating the ROS/GPX4-mediated ferroptosis pathway, providing a new strategy and target for the treatment of FLHS.
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- 2024
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13. Structure-based discovery of small molecules that disaggregate Alzheimer’s disease tissue derived tau fibrils in vitro
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Paul M. Seidler, Kevin A. Murray, David R. Boyer, Peng Ge, Michael R. Sawaya, Carolyn J. Hu, Xinyi Cheng, Romany Abskharon, Hope Pan, Michael A. DeTure, Christopher K. Williams, Dennis W. Dickson, Harry V. Vinters, and David S. Eisenberg
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Science - Abstract
Evidence suggests that fibrous aggregates of protein tau may be the proximal cause of Alzheimer’s disease. Here, using atomic structures of tau fibrils from brains of people with Alzheimer’s disease, the authors have found small-molecule drug leads that disaggregate tau fibrils in vitro.
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- 2022
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14. Blunting ROS/TRPML1 pathway protects AFB1-induced porcine intestinal epithelial cells apoptosis by restoring impaired autophagic flux
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Xinyi Cheng, Jiahua Liang, Dan Wu, Xiaoquan Guo, Huabin Cao, Caiying Zhang, Ping Liu, Ruiming Hu, Guoliang Hu, and Yu Zhuang
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Aflatoxin B1 ,TRPML1 ,ROS ,Autophagic flux ,Apoptosis ,Environmental pollution ,TD172-193.5 ,Environmental sciences ,GE1-350 - Abstract
Aflatoxin B1 (AFB1) is a stable mycotoxin that contaminates animal feed on a large scale and causes severe damage to intestinal cells, induces inflammation and stimulates autophagy. Transient receptor potential mucolipin subfamily 1 (TRPML1) is a regulatory factor of autophagy, but the underlying mechanisms of TRPML1-mediated autophagy in AFB1 intestine toxicity remain elucidated. In the present study, AFB1 (0, 5, 10 μg/mL) was shown to reduce cell viability, increase reactive oxygen species (ROS) accumulation and apoptosis rate. Additionally, AFB1 caused structural damage to mitochondria and lysosomes and increased autophagosomes numbers. Furthermore, AFB1 promoted Ca2+ release by activating the TRPML1 channel, stimulated the expression of autophagy-related proteins, and induced autophagic flux blockade. Moreover, pharmacological inhibition of autophagosome formation by 3-methyladenine attenuated AFB1-induced apoptosis by downregulating the levels of TRPML1 and ROS, whereas blockade of autophagosome-lysosomal fusion by chloroquine alleviated AFB1-induced apoptosis by upregulating TRPML1 expression and exacerbating ROS accumulation. Intriguingly, blocking AFB1-induced autophagic flux generated ROS- and TRPML1-dependent cell death, as shown by the decreased apoptosis in the presence the free radical scavenger N-Acetyl-L-cysteine and the TRPML1 inhibitor ML-SI1. Overall, these results showed that AFB1 promoted apoptosis of IPEC-J2 cells by disrupting autophagic flux through activation of the ROS/TRPML1 pathway.
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- 2023
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15. TIL-Derived CAR T Cells Improve Immune Cell Infiltration and Survival in the Treatment of CD19-Humanized Mouse Colorectal Cancer
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Can Zhu, Yuanyuan Zhao, Jiaheng He, Huan Zhao, Li Ni, Xinyi Cheng, Yida Chen, Liqian Mu, Xiaojun Zhou, Qin Shi, and Jie Sun
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immunotherapy ,tumor-infiltrating T cell ,CAR T ,colorectal cancer ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Chimeric antigen receptor-engineered T cells (CAR Ts) targeting CD19 have shown unprecedented prognosis in treating hematological cancers. However, the lack of a tumor-specific antigen as the target and an inhospitable tumor environment limit the clinical application of CAR T in solid tumors. Tumor-infiltrating T lymphocytes (TIL) exhibit diverse T cell receptor clonality and superior tumor-homing abilities. Therefore, in our study, human CD19-target TIL CAR-Ts armed with CD3ζ and 4-1BB signaling domains were constructed. Mouse colorectal cancer CT26 cells expressing human CD19 (hCD19+-CT26) were developed to assess the anti-tumor activity of TIL CAR-T cells, both in vitro and in vivo. Compared with splenic CAR T adoptive transfer, TIL CAR-T administration showed superior tumor suppression ability in hCD19+-CT26 tumor-bearing mice. Furthermore, more T cells were found at the tumor site and had lower exhaustion-related inhibitory receptor (T cell immunoglobulin and mucin domain-containing protein 3, Tim3) expression and higher immune memory molecule (CD62L) expression. Overall, we provided an artificial tumor-specific antigen in solid tumors and demonstrated that combined CAR-expressing TIL-Ts (TIL CAR-Ts) exhibited strong anti-tumor activity, with improved T cell infiltration and immune memory. Our humanized tumor antigen presented platform of mice suggests that TIL CAR-T-based adoptive therapy could be a promising strategy for solid cancer treatment.
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- 2023
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16. Metagenomic insights into the functions of microbial communities in sulfur-rich sediment of a shallow-water hydrothermal vent off Kueishan Island
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Li Wang, Ziyi Shen, Xinyi Cheng, Jiang-Shiou Hwang, Yizhe Guo, Mingye Sun, Junwei Cao, Rulong Liu, and Jiasong Fang
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Campylobacteria ,shallow-water hydrothermal vent ,sulfur cycle ,sediment ,metagenome-assembled-genomes ,Kueishan Island ,Microbiology ,QR1-502 - Abstract
Hydrothermal vent (HTV) systems are important habitats for understanding the biological processes of extremophiles on Earth and their relative contributions to material and energy cycles in the ocean. Current understanding on hydrothermal systems have been primarily focused on deep-sea HTVs, and little is known about the functions and metabolisms of microorganisms in shallow-water HTVs (SW-HTVs), which are distinguished from deep-sea HTVs by a depth limit of 200 m. In this study, we analyzed metagenomes of sulfur-rich sediment samples collected from a SW-HTV of Kueishan Island, located in a marginal sea of the western Pacific Ocean. Comparing with a previously published report of pelagic samples from the nearby sampling site, microbial communities in the SW-HTV sediments enriching with genes of both aerobic and anaerobic respiration inferred variable environments in the tested sediments. Abundant genes of energy metabolism encoding sulfur oxidation, H2 oxidation, and carbon fixation were detected from the sediment samples. Sixty-eight metagenome-assembled-genomes (MAGs) were reconstructed to further understand the metabolism and potential interactions between different microbial taxa in the SW-HTVs sediment. MAGs with the highest abundant were chemolithotrophic sulfur-oxidization bacteria, including Sulfurovum represented Campylobacteria involved sox multienzyme, sulfide oxidation genes and rTCA cycle, and Gammaproteobacteria involved dsr gene and CBB cycle. In addition, Desulfobacterota with the potential to participate in sulfur-disproportionating processes also had higher abundance than the sample’s overall mean value. The interaction of these bacterial groups allows the microbial communities to efficiently metabolize a large variety of sulfur compounds. In addition, the potential to use simple organic carbon, such as acetate, was found in chemolithotrophic Campylobacterial MAGs. Collectively, our results revealed the complexity of environmental conditions of the vent sediment and highlight the interactive relationships of the dominant microbial populations in driving sulfur cycles in the SW-HTV sediments off Kueishan Island.
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- 2022
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17. Organozinc pivalates for cobalt-catalyzed difluoroalkylarylation of alkenes
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Xinyi Cheng, Xingchen Liu, Shengchun Wang, Ying Hu, Binjing Hu, Aiwen Lei, and Jie Li
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Science - Abstract
Transition metal-catalyzed regioselective difunctionalizations of alkenes with two different functional groups are useful for preparing organic compounds, but the construction of two new C–C bonds is challenging. Here, the authors report cobalt-catalyzed regioselective difluoroalkylarylation of alkenes with solid arylzinc pivalates and difluoroalkyl bromides, through a cascade Csp3 ‒Csp3/Csp3 ‒Csp2 bond formation.
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- 2021
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18. Baicalin Attenuates H2O2-Induced Oxidative Stress by Regulating the AMPK/Nrf2 Signaling Pathway in IPEC-J2 Cells
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Jiahua Liang, Ying Zhou, Xinyi Cheng, Jiaqi Chen, Huabin Cao, Xiaoquan Guo, Caiying Zhang, Yu Zhuang, and Guoliang Hu
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baicalin ,oxidative stress ,IPEC-J2 cell ,AMPK-mediated antioxidant defense ,apoptosis ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
Oxidative stress can adversely affect the health status of the body, more specifically by causing intestinal damage by disrupting the permeability of the intestinal barrier. This is closely related to intestinal epithelial cell apoptosis caused by the mass production of reactive oxygen species (ROS). Baicalin (Bai) is a major active ingredient in Chinese traditional herbal medicine that has antioxidant, anti-inflammatory, and anti-cancer properties. The purpose of this study was to explore the underlying mechanisms by which Bai protects against hydrogen peroxide (H2O2)-induced intestinal injury in vitro. Our results indicated that H2O2 treatment caused injury to IPEC-J2 cells, resulting in their apoptosis. However, Bai treatment attenuated H2O2-induced IPEC-J2 cell damage by up-regulating the mRNA and protein expression of ZO-1, Occludin, and Claudin1. Besides, Bai treatment prevented H2O2-induced ROS and MDA production and increased the activities of antioxidant enzymes (SOD, CAT, and GSH-PX). Moreover, Bai treatment also attenuated H2O2-induced apoptosis in IPEC-J2 cells by down-regulating the mRNA expression of Caspase-3 and Caspase-9 and up-regulating the mRNA expression of FAS and Bax, which are involved in the inhibition of mitochondrial pathways. The expression of Nrf2 increased after treatment with H2O2, and Bai can alleviate this phenomenon. Meanwhile, Bai down-regulated the ratio of phosphorylated AMPK to unphosphorylated AMPK, which is indicative of the mRNA abundance of antioxidant-related genes. In addition, knockdown of AMPK by short-hairpin RNA (shRNA) significantly reduced the protein levels of AMPK and Nrf2, increased the percentage of apoptotic cells, and abrogated Bai-mediated protection against oxidative stress. Collectively, our results indicated that Bai attenuated H2O2-induced cell injury and apoptosis in IPEC-J2 cells through improving the antioxidant capacity through the inhibition of the oxidative stress-mediated AMPK/Nrf2 signaling pathway.
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- 2023
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19. Large-Scale Genomic Epidemiology of Klebsiella pneumoniae Identified Clone Divergence with Hypervirulent Plus Antimicrobial-Resistant Characteristics Causing Within-Ward Strain Transmissions
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Na Pei, Yanming Li, Chunjiao Liu, Zijuan Jian, Tianzhu Liang, Yiming Zhong, Wanying Sun, Jingxuan He, Xinyi Cheng, Hongling Li, Xiaole Lei, Xin Liu, Ziqing Deng, Qingxia Liu, Xia Chen, Qun Yan, Karsten Kristiansen, Junhua Li, and Wenen Liu
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clone divergence ,genomic epidemiology ,Klebsiella pneumoniae ,nosocomial transmission ,Microbiology ,QR1-502 - Abstract
ABSTRACT Global dissemination of K. pneumoniae clones poses health hazards to the public. Genomic epidemiology studies with comprehensive data set further revealed clone divergence, showing a high complexity in evolution. Moreover, clones carrying both acquired virulent and antimicrobial-resistant genes emerged and might replace the carbapenem-resistant clones. Co-occurrence of virulence and resistance is emerging. An unbiased collection of 3,061 clinical K. pneumoniae isolates (January 5, 2013 to July 24, 2018) underwent whole-genome sequencing. Pairwise core-genome single-nucleotide polymorphism (cgSNP) distances identified clone divergence and transmission events. A sum of 2,193 nonduplicated genomes clustered into four phenotypically indistinguishable species complexes. 93% (n = 2,035) were KpI with its largest clonal group (CG) being CG11 (n = 406). Three hundred ninety-three were ST11 and three hundred seventy-four carried blaKPC-2. Noticeably, CG11 is divided into two main subclones based on the capsule synthesis K loci (KL). CG11-KL64 showed a clear hypervirulent plus antimicrobial-resistant (hv+AMR) characteristic. Besides, the phylogenetic structure revealed the clone divergence of CG25, and this is the first report with sufficient CG25 genomes to identify the divergence. The outcomes of the hv+AMR CG25 cluster 1 affected patients were poorer (P < 0.05). Moreover, two episodes of strain transmissions were associated with CG25 cluster 1. Other transmissions were associated with ST20 and ST307. Genomic epidemiology identified clone divergence of CG11 and CG25. The hv+AMR subclones pose greater threats on a global scale. Nosocomial transmissions of the high-risk clones raised our concerns about the evolution and transmission of emerging clones among newborns and critically ill patients. IMPORTANCE The convergence of AMR and acquired virulence posing higher risks to the public is a focusing point. With sufficient genomes and genotypes, we successfully identify the convergence in two subclones, the previously reported CG11-KL64, and the newly reported CG25 cluster 1. The novel finding of the CG25 divergence was not only revealed by the phylogenetic tree but also confirmed by the clinical outcome data and the accessory genome patterns. Moreover, the transmission subclones circulated in two clinically important wards highlights the deficiency of infection control program using conventional methods. Without the assistance of whole-genome sequencing, the transmissions of high-risk clones could not be identified.
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- 2022
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20. Intra-host variation and evolutionary dynamics of SARS-CoV-2 populations in COVID-19 patients
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Yanqun Wang, Daxi Wang, Lu Zhang, Wanying Sun, Zhaoyong Zhang, Weijun Chen, Airu Zhu, Yongbo Huang, Fei Xiao, Jinxiu Yao, Mian Gan, Fang Li, Ling Luo, Xiaofang Huang, Yanjun Zhang, Sook-san Wong, Xinyi Cheng, Jingkai Ji, Zhihua Ou, Minfeng Xiao, Min Li, Jiandong Li, Peidi Ren, Ziqing Deng, Huanzi Zhong, Xun Xu, Tie Song, Chris Ka Pun Mok, Malik Peiris, Nanshan Zhong, Jingxian Zhao, Yimin Li, Junhua Li, and Jincun Zhao
- Subjects
SARS-CoV-2 ,COVID-19 ,Intra-host ,Variation ,Dynamics ,Medicine ,Genetics ,QH426-470 - Abstract
Abstract Background Since early February 2021, the causative agent of COVID-19, SARS-CoV-2, has infected over 104 million people with more than 2 million deaths according to official reports. The key to understanding the biology and virus-host interactions of SARS-CoV-2 requires the knowledge of mutation and evolution of this virus at both inter- and intra-host levels. However, despite quite a few polymorphic sites identified among SARS-CoV-2 populations, intra-host variant spectra and their evolutionary dynamics remain mostly unknown. Methods Using high-throughput sequencing of metatranscriptomic and hybrid captured libraries, we characterized consensus genomes and intra-host single nucleotide variations (iSNVs) of serial samples collected from eight patients with COVID-19. The distribution of iSNVs along the SARS-CoV-2 genome was analyzed and co-occurring iSNVs among COVID-19 patients were identified. We also compared the evolutionary dynamics of SARS-CoV-2 population in the respiratory tract (RT) and gastrointestinal tract (GIT). Results The 32 consensus genomes revealed the co-existence of different genotypes within the same patient. We further identified 40 intra-host single nucleotide variants (iSNVs). Most (30/40) iSNVs presented in a single patient, while ten iSNVs were found in at least two patients or identical to consensus variants. Comparing allele frequencies of the iSNVs revealed a clear genetic differentiation between intra-host populations from the respiratory tract (RT) and gastrointestinal tract (GIT), mostly driven by bottleneck events during intra-host migrations. Compared to RT populations, the GIT populations showed a better maintenance and rapid development of viral genetic diversity following the suspected intra-host bottlenecks. Conclusions Our findings here illustrate the intra-host bottlenecks and evolutionary dynamics of SARS-CoV-2 in different anatomic sites and may provide new insights to understand the virus-host interactions of coronaviruses and other RNA viruses.
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- 2021
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21. Baicalin ameliorates APEC-induced intestinal injury in chicks by inhibiting the PI3K/AKT-mediated NF-κB signaling pathway
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Xinyi Cheng, Zhanyou Cao, Junrong Luo, Ruiming Hu, Huabin Cao, Xiaoquan Guo, Chenghong Xing, Fan Yang, Yu Zhuang, and Guoliang Hu
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Baicalin ,avian pathogenic Escherichia coli ,intestinal injury ,PI3K/AKT/NF-κB, chick ,Animal culture ,SF1-1100 - Abstract
ABSTRACT: Avian pathogenic Escherichia coli (APEC) is the causative agent of avian colibacillosis. Baicalin (BA) possesses multiple pharmacological effects, but the mechanism underlying its activity in APEC-induced intestinal injury remains unknown. This study aims to investigate the protective effects and possible mechanism of BA against APEC-induced intestinal injury. Sixty 1-day-old chicks were randomly divided into 4 groups: the control group (basal diet), E. coli group (basal diet), BAI10 group (10 mg/kg BA), and BAI20 group (20 mg/kg BA). After pretreatment with BA for 15 d and subsequent induction of APEC infection by pectoralis injection, the ileum was collected and analyzed. The results showed that BA-pretreatment demonstrated an alleviation of chicks in diarrhea rate, mortality, and histopathological changes in intestinal tissues after APEC infection. Additionally, following APEC infection, BA improved the intestinal barrier by elevating zona occludens (ZO)s (ZO-1, 2, 3), Claudins (Claudin1, 2, 3), Occludin, avian β-defensin (AvBD)s (AvBD1, 2, 4), lysozyme (Lyz) mRNA levels and ZO-1, Claudin1, and Occludin protein levels. Besides, the activities of total superoxide dismutase (T-SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) and the SOD-1 and CAT mRNA levels and SOD-1 protein level were elevated by BA pretreatment. BA pretreatment also decreased the malondialdehyde (MDA) content, heme oxygenase-1 (HO-1) and NADH quinone oxidoreductase 1 (NQO1) mRNA levels, and HO-1 protein level after APEC infection. BA alleviated the APEC-induced inflammatory response, including downregulating the mRNA levels of proinflammatory cytokines (tumor necrosis factor-α (TNF-α), interleukin [IL]-1β, IL-6, IL-8) and upregulating the mRNA levels of anti-inflammatory cytokines (IL-4, IL-10, IL-13, transforming growth factor-β [TGF-β]). Furthermore, BA decreased the mRNA and protein levels of phosphatidylinositol 3 kinase (PI3K), protein kinase B (AKT), and nuclear factor kappa-B (NF-κB) as well as the expression of the phosphorylated forms of these proteins after APEC infection. Collectively, our findings indicate that BA exerts a protective effect against APEC-induced intestinal injury in chicks by inhibiting the PI3K/AKT-mediated NF-κB pathway, suggesting that BA may be a potential therapeutic approach for avian colibacillosis.
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- 2022
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22. Multiple approaches for massively parallel sequencing of SARS-CoV-2 genomes directly from clinical samples
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Minfeng Xiao, Xiaoqing Liu, Jingkai Ji, Min Li, Jiandong Li, Lin Yang, Wanying Sun, Peidi Ren, Guifang Yang, Jincun Zhao, Tianzhu Liang, Huahui Ren, Tian Chen, Huanzi Zhong, Wenchen Song, Yanqun Wang, Ziqing Deng, Yanping Zhao, Zhihua Ou, Daxi Wang, Jielun Cai, Xinyi Cheng, Taiqing Feng, Honglong Wu, Yanping Gong, Huanming Yang, Jian Wang, Xun Xu, Shida Zhu, Fang Chen, Yanyan Zhang, Weijun Chen, Yimin Li, and Junhua Li
- Subjects
Emerging infectious diseases ,COVID-19 ,Metatranscriptomic sequencing ,Hybrid capture ,Multiplex PCR ,iSNV ,Medicine ,Genetics ,QH426-470 - Abstract
Abstract Background COVID-19 (coronavirus disease 2019) has caused a major epidemic worldwide; however, much is yet to be known about the epidemiology and evolution of the virus partly due to the scarcity of full-length SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) genomes reported. One reason is that the challenges underneath sequencing SARS-CoV-2 directly from clinical samples have not been completely tackled, i.e., sequencing samples with low viral load often results in insufficient viral reads for analyses. Methods We applied a novel multiplex PCR amplicon (amplicon)-based and hybrid capture (capture)-based sequencing, as well as ultra-high-throughput metatranscriptomic (meta) sequencing in retrieving complete genomes, inter-individual and intra-individual variations of SARS-CoV-2 from serials dilutions of a cultured isolate, and eight clinical samples covering a range of sample types and viral loads. We also examined and compared the sensitivity, accuracy, and other characteristics of these approaches in a comprehensive manner. Results We demonstrated that both amplicon and capture methods efficiently enriched SARS-CoV-2 content from clinical samples, while the enrichment efficiency of amplicon outran that of capture in more challenging samples. We found that capture was not as accurate as meta and amplicon in identifying between-sample variations, whereas amplicon method was not as accurate as the other two in investigating within-sample variations, suggesting amplicon sequencing was not suitable for studying virus-host interactions and viral transmission that heavily rely on intra-host dynamics. We illustrated that meta uncovered rich genetic information in the clinical samples besides SARS-CoV-2, providing references for clinical diagnostics and therapeutics. Taken all factors above and cost-effectiveness into consideration, we proposed guidance for how to choose sequencing strategy for SARS-CoV-2 under different situations. Conclusions This is, to the best of our knowledge, the first work systematically investigating inter- and intra-individual variations of SARS-CoV-2 using amplicon- and capture-based whole-genome sequencing, as well as the first comparative study among multiple approaches. Our work offers practical solutions for genome sequencing and analyses of SARS-CoV-2 and other emerging viruses.
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- 2020
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23. Luteolin Attenuates APEC-Induced Oxidative Stress and Inflammation via Inhibiting the HMGB1/TLR4/NF-κB Signal Axis in the Ileum of Chicks
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Zhanyou Cao, Chenghong Xing, Xinyi Cheng, Junrong Luo, Ruiming Hu, Huabin Cao, Xiaoquan Guo, Fan Yang, Yu Zhuang, and Guoliang Hu
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luteolin ,intestinal injure ,APEC ,HMGB1 ,NF-κB ,chick ,Veterinary medicine ,SF600-1100 ,Zoology ,QL1-991 - Abstract
Avian pathogenic E. coli (APEC) is typically the cause of avian colibacillosis, which can result in oxidative stress, inflammation, and intestinal damage (APEC). Luteolin, in the form of glycosylation flavone, has potent anti-inflammatory and anti-oxidative properties. However, its effects on APEC-induced intestinal oxidative stress and NF-κB-mediated inflammation in chicks remains poorly understood. After hatching, one-day-old chicks were stochastically assigned to four groups: a control group (basic diet), an E. coli group (basic diet) and L10 and L20 groups (with a dry matter of luteolin diet 10 mg/kg and 20 mg/kg, respectively), with fifteen chicks in each group and one repeat per group. They were pretreated for thirteen days. The body weight, mortality, histopathological changes in the ileum, antioxidant status, and the mRNA and protein-expression levels of factors associated with the HMGB1/TLR4/NF-κB signal axis of the chicks were measured. The results showed that luteolin treatment decreased the mRNA and protein-expression level of the related factors of HMGB1/TLR4/NF-κB signal axis in the ileum, reduced inflammation, increased antioxidant enzyme activity, and reduced intestinal injury. Collectively, luteolin alleviated APEC-induced intestinal damage by means of hindering the HMGB1/TLR4/NF-κB signal axis, which suggests that luteolin could be a good method for the prevention and treatment of avian colibacillosis.
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- 2022
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24. Population Bottlenecks and Intra-host Evolution During Human-to-Human Transmission of SARS-CoV-2
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Daxi Wang, Yanqun Wang, Wanying Sun, Lu Zhang, Jingkai Ji, Zhaoyong Zhang, Xinyi Cheng, Yimin Li, Fei Xiao, Airu Zhu, Bei Zhong, Shicong Ruan, Jiandong Li, Peidi Ren, Zhihua Ou, Minfeng Xiao, Min Li, Ziqing Deng, Huanzi Zhong, Fuqiang Li, Wen-jing Wang, Yongwei Zhang, Weijun Chen, Shida Zhu, Xun Xu, Xin Jin, Jingxian Zhao, Nanshan Zhong, Wenwei Zhang, Jincun Zhao, Junhua Li, and Yonghao Xu
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SARS-CoV-2 ,population bottleneck ,intra-host variation ,human to human transmission ,evolution ,Medicine (General) ,R5-920 - Abstract
The emergence of the novel human coronavirus, SARS-CoV-2, causes a global COVID-19 (coronavirus disease 2019) pandemic. Here, we have characterized and compared viral populations of SARS-CoV-2 among COVID-19 patients within and across households. Our work showed an active viral replication activity in the human respiratory tract and the co-existence of genetically distinct viruses within the same host. The inter-host comparison among viral populations further revealed a narrow transmission bottleneck between patients from the same households, suggesting a dominated role of stochastic dynamics in both inter-host and intra-host evolutions.
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- 2021
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25. Watershed Eco-Compensation Mechanism in China: Policies, Practices and Recommendations
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Xinyi Cheng, Lan Fang, Lan Mu, Jun Li, and Heng Wang
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watershed ,watershed eco-compensation mechanism ,policy ,legal basis ,China ,Hydraulic engineering ,TC1-978 ,Water supply for domestic and industrial purposes ,TD201-500 - Abstract
Watershed eco-compensation (WEC) is considered a significant environmental policy instrument for watershed ecological protection and management. However, in the legislation and practice of eco-compensation in China, the development of the WEC mechanism is still in the initial stages. In this paper, the institutional opportunities and challenges of WEC are analyzed from the existing policies, laws, and economical instruments. Theoretically, WEC in China has seen a combination of punitive-based “Watershed Ecological Damage Compensation (WEDC)” and incentive-based “Watershed Ecological Protective Compensation (WEPC)”. Through a comparative analysis of domestic and foreign watershed compensation practices, the results demonstrate that most of China’s WEC projects have an insufficient legal basis, a single compensatory subject, insufficient compensation funds, and an imperfect market-oriented compensation mechanism. To improve watershed eco-compensation in China, it is recommended to strengthen legislation, select diversified eco-compensation approaches, and establish a market-based and systematic eco-compensation mechanism for watersheds.
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- 2022
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26. A smart city used low-latency seamless positioning system based on inverse global navigation satellite system technology
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Deyue Zou, Shutong Niu, Shuhao Chen, Binhong Su, Xinyi Cheng, Jie Liu, Yunfeng Liu, and Yang Li
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Electronic computers. Computer science ,QA75.5-76.95 - Abstract
People have to move between indoor and outdoor frequently in city scenarios. The global navigation satellite system signal cannot provide reliable indoor positioning services. To solve the problem, this article proposes a seamless positioning system based on an inverse global navigation satellite system signal, which can extend the global navigation satellite system service into the indoor scenario. In this method, a signal source is arranged at a key position in the room, and the inverse global navigation satellite system signal is transmitted to the global navigation satellite system receiver to obtain a preset positioning result. The indoor positioning service is continued with the inertial navigation system after leaving the key position. The inverse global navigation satellite system seamless positioning system proposed in this article can unify indoor and outdoor positioning using the same receiver. The receiver does not need to re-receive navigation information when the scene changes, which avoids the switching process. Through the design of signal layer coverage, the receiver is in a warm start state, and the users can quickly fix the position when the scenario changes, realizing quick access in a true sense. This enables the ordinary commercial global navigation satellite system receiver to obtain indoor positioning capability without modification, and the algorithm can perform accurate positioning indoors and outdoors without switching.
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- 2019
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27. Application of Interactive Installation Art Design Based on Generalization Theory.
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Lin Liu, Yue Mi, Xinyi Cheng, and Yu Shi
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- 2024
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28. Pseudo-Noise Code Shifting Signal for AI Arranged UAV Networking.
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Deyue Zou, Jie Liu, Xinyi Cheng, Jing Zhang, Yunfeng Liu 0001, and Shouchuan Ma
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- 2020
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29. Orbit determination algorithm and performance analysis of high-orbit spacecraft based on GNSS.
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Deyue Zou, Qi Zhang, Yongen Cui, Yunfeng Liu 0001, Jing Zhang, Xinyi Cheng, and Jie Liu
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- 2019
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30. Analysis and Improvement Research of Home Property Insurance Under the Trend of Smart Home
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Xinyi Cheng
- Abstract
Although home insurance is one of the earliest property insurance types in China, its development has been unsatisfactory. At present, the coverage rate of household insurance in China is less than 10%, accounting for less than 1% of the total premium of property insurance. Therefore, the research topic of this paper is the analysis and improvement research of home property insurance under the trend of smart homes. The main contents of the study are as follows. Home property insurance products and existing problems under the condition of existing insurance technology- the form of services about insurance is singular and less attractive than the insurance. The second is to introduce a new product and it can improve the present situation in these aspects- the probability of property loss and the number of property losses will be reduced and moral hazard decreases. The final part is the analysis of the way that the new product solves the problem- customization of underwriting content and intelligent loss settlement.
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- 2023
31. Chemical characterization and solvent fractionation of tilapia oil for its potential application as human milk fat substitute
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Xinyi Cheng, Zhuoneng Huang, Qingzhe Jin, and Xiaosan Wang
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Milk, Human ,Solvents ,Infant ,Animals ,Humans ,Fat Substitutes ,Triglycerides ,Tilapia ,Food Science - Abstract
The natural source of human milk fat substitute (HMFS) is a field worth exploring. In this study, tilapia oil was extracted and analyzed. In the triacylglycerol fraction, the contents of sn-2 palmitic acid and total sn-1,3 oleic acid and linoleic acid were 48.01% and 66.62%, respectively. The optimal solvent fractionation conditions were determined to be a tilapia oil-to-acetone ratio of 1:8 (w/v), crystallization temperature of -30°C, and crystallization duration of 16 h, giving a solid fraction yield of 64.20%. In fractionated tilapia oil, the total content of 1-oleoyl-2-palmitoyl-3-linoleoylglycerol (OPL) and 1,3-dioleoyl-2-palmitoylglycerol (OPO) increased by 20.38%, as determined by reversed-phase liquid chromatography. Ultra-high-performance combined-phase chromatography combined with quadrupole time-of-flight mass spectrometry analysis showed that OPL (17.45%) was the most abundant triacylglycerol in fractionated tilapia oil, followed by OPO (13.90%). Fractionated tilapia oil is thus an excellent source of OPL and has great potential for incorporation in HMFS. PRACTICAL APPLICATION: Human milk fat substitutes are an important component of infant formulas. This work provides an excellent natural source of oil rich in OPL, which has great potential in the field of preparing human milk fat substitutes highly similar to human milk fat.
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- 2022
32. Structure-based design of nanobodies that inhibit seeding of Alzheimer’s patient–extracted tau fibrils.
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Abskharon, Romany, Pan, Hope, Sawaya, Michael R., Seidler, Paul M., Olivares, Eileen J., Yu Chen, Murray, Kevin A., Jeffrey Zhang, Lantz, Carter, Bentzel, Megan, Boyer, David R., Cascio, Duilio, Nguyen, Binh A., Hou, Ke, Xinyi Cheng, Pardon, Els, Williams, Christopher K., Nana, Alissa L., Vinters, Harry V., and Spina, Salvatore
- Subjects
ALZHEIMER'S disease ,TAU proteins ,IMMUNOGLOBULINS ,PROGRESSIVE supranuclear palsy ,SYNTHETIC antibodies - Abstract
Despite much effort, antibody therapies for Alzheimer’s disease (AD) have shown limited efficacy. Challenges to the rational design of effective antibodies include the difficulty of achieving specific affinity to critical targets, poor expression, and antibody aggregation caused by buried charges and unstructured loops. To overcome these challenges, we grafted previously determined sequences of fibril-capping amyloid inhibitors onto a camel heavy chain antibody scaffold. These sequences were designed to cap fibrils of tau, known to form the neurofibrillary tangles of AD, thereby preventing fibril elongation. The nanobodies grafted with capping inhibitors blocked tau aggregation in biosensor cells seeded with postmortem brain extracts from AD and progressive supranuclear palsy (PSP) patients. The tau capping nanobody inhibitors also blocked seeding by recombinant tau oligomers. Another challenge to the design of effective antibodies is their poor blood–brain barrier (BBB) penetration. In this study, we also designed a bispecific nanobody composed of a nanobody that targets a receptor on the BBB and a tau capping nanobody inhibitor, conjoined by a flexible linker. We provide evidence that the bispecific nanobody improved BBB penetration over the tau capping inhibitor alone after intravenous administration in mice. Our results suggest that the design of synthetic antibodies that target sequences that drive protein aggregation may be a promising approach to inhibit the prion-like seeding of tau and other proteins involved in AD and related proteinopathies. [ABSTRACT FROM AUTHOR]
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- 2023
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33. Material Application and Structural Features in the Design of Sales Packaging
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Lin Liu and Xinyi Cheng
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- 2023
34. Effects of immersion freezing methods on water holding capacity, ice crystals and water migration in grass carp during frozen storage
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Wenshui Xia, Xinyi Cheng, Lishi Wang, and Yuduan Diao
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Animal science ,biology ,Ice crystals ,Chemistry ,Mechanical Engineering ,Immersion (virtual reality) ,Water holding capacity ,Building and Construction ,Frozen storage ,biology.organism_classification ,Freezing methods ,Grass carp - Published
- 2021
35. Simultaneous serotonin and dopamine monitoring across timescales by rapid pulse voltammetry with partial least squares regression
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Katie A Perrotta, Anne M. Andrews, Miguel Alcañiz Fillol, Hongyan Yang, Rahul Iyer, Xinyi Cheng, Merel Dagher, and Cameron S Movassaghi
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Serotonin ,Analyte ,Dopamine ,Capacitive sensing ,Biochemistry ,Analytical Chemistry ,TECNOLOGIA ELECTRONICA ,Machine Learning ,Escitalopram ,Carbon Fiber ,In vivo ,Partial least squares regression ,Electrochemistry ,medicine ,Animals ,Least-Squares Analysis ,Voltammetry ,Neurotransmitter Agents ,Background subtraction ,Chemistry ,Pulse (signal processing) ,Brain ,Signal Processing, Computer-Assisted ,Electrochemical Techniques ,Neurotransmitters ,Mice, Inbred C57BL ,Calibration ,Female ,Biological system ,Microelectrodes ,Selective Serotonin Reuptake Inhibitors ,Software ,Research Paper ,medicine.drug - Abstract
[EN] Many voltammetry methods have been developed to monitor brain extracellular dopamine levels. Fewer approaches have been successful in detecting serotonin in vivo. No voltammetric techniques are currently available to monitor both neurotransmitters simultaneously across timescales, even though they play integrated roles in modulating behavior. We provide proof-of-concept for rapid pulse voltammetry coupled with partial least squares regression (RPV-PLSR), an approach adapted from multi-electrode systems (i.e., electronic tongues) used to identify multiple components in complex environments. We exploited small differences in analyte redox profiles to select pulse steps for RPV waveforms. Using an intentionally designed pulse strategy combined with custom instrumentation and analysis software, we monitored basal and stimulated levels of dopamine and serotonin. In addition to faradaic currents, capacitive currents were important factors in analyte identification arguing against background subtraction. Compared to fast-scan cyclic voltammetry-principal components regression (FSCV-PCR), RPV-PLSR better differentiated and quantified basal and stimulated dopamine and serotonin associated with striatal recording electrode position, optical stimulation frequency, and serotonin reuptake inhibition. The RPV-PLSR approach can be generalized to other electrochemically active neurotransmitters and provides a feedback pipeline for future optimization of multi-analyte, fit-for-purpose waveforms and machine learning approaches to data analysis., Funding from the National Institute on Drug Abuse (DA045550) and National Institute of Mental Health (MH106806) was received. CSM was supported by the National Science Foundation Graduate Research Fellowship Program (DGE-1650604 and DGE-2034835). Any opinions, findings, and conclusions or recommendations expressed in this material are those of the authors and do not necessarily reflect the views of the National Science Foundation.
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- 2021
36. Enhancing YOLOv3-tiny for Mask Detection in Natural Scenes
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Xinyi Cheng, Jiale Wang, and Simkuan Goh
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- 2022
37. Oxygen-Sensitive MRI: A Predictive Imaging Biomarker for Tumor Radiation Response?
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Strahinja Stojadinovic, Ralph P. Mason, Tsuicheng Chiu, Tatsuya J. Arai, Xinyi Cheng, Peter Peschke, Donghan M. Yang, and James W. Campbell
- Subjects
Male ,Cancer Research ,Time Factors ,Imaging biomarker ,chemistry.chemical_element ,Radiation Tolerance ,Oxygen ,Article ,030218 nuclear medicine & medical imaging ,03 medical and health sciences ,0302 clinical medicine ,Prostate ,medicine ,Animals ,Radiology, Nuclear Medicine and imaging ,Irradiation ,Radiation ,Tumor hypoxia ,medicine.diagnostic_test ,business.industry ,Air ,Prostatic Neoplasms ,Dose-Response Relationship, Radiation ,Radiotherapy Dosage ,Magnetic resonance imaging ,Cone-Beam Computed Tomography ,Hypoxia (medical) ,Prognosis ,Magnetic Resonance Imaging ,Rats ,medicine.anatomical_structure ,Oncology ,chemistry ,030220 oncology & carcinogenesis ,Breathing ,Tumor Hypoxia ,medicine.symptom ,Nuclear medicine ,business ,Biomarkers ,Neoplasm Transplantation ,Radiotherapy, Image-Guided - Abstract
PURPOSE: To develop a non-invasive prognostic imaging biomarker related to hypoxia to predict stereotactic ablation radiation therapy (SAbR) tumor control. METHODS AND MATERIALS: One hundred and forty-five subcutaneous syngeneic Dunning prostate R3327-AT1 rat tumors were focally irradiated once using CBCT guidance on a small animal irradiator at 225 kV. Various doses in the range 0–100 Gy were administered, while rats breathed air or oxygen and tumor control was assessed up to 200 days. Oxygen-sensitive MRI (T(1)-weighted, ΔR(1), ΔR(2)*) was applied to 79 of these tumors at 4.7 T to assess response to an oxygen gas breathing challenge on the day before irradiation as a probe of tumor hypoxia. RESULTS: Increasing radiation dose in the range 0–90 Gy enhanced tumor control of air-breathing rats with a TCD(50) estimated at 59.6±1.5 Gy. Control was significantly improved at some doses when rats breathed oxygen during irradiation (e.g., 40 Gy, p0.922 with O(2)-gas breathing challenge showed significantly better control at 40 Gy, when irradiated while breathing oxygen (75% vs. 0%, p0.922 revealed different survival curves with TCD(50)=36.2±3.2 Gy for tumors responsive to oxygen gas breathing challenge, which was significantly less than 54.7±2.4 Gy for unresponsive tumors (p
- Published
- 2021
38. De novo designed protein inhibitors of amyloid aggregation and seeding
- Author
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Kevin A. Murray, Carolyn J. Hu, Sarah L. Griner, Hope Pan, Jeannette T. Bowler, Romany Abskharon, Gregory M. Rosenberg, Xinyi Cheng, Paul M. Seidler, and David S. Eisenberg
- Subjects
Amyloid ,Aging ,alpha-synuclein ,tau Proteins ,Neurodegenerative ,Alzheimer's Disease ,Protein Aggregation, Pathological ,Alzheimer Disease ,Pathological ,Acquired Cognitive Impairment ,Humans ,2.1 Biological and endogenous factors ,tau ,Aetiology ,protein design ,Amyloid beta-Peptides ,Parkinson's Disease ,Multidisciplinary ,Neurosciences ,Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD) ,Parkinson Disease ,Amyloidosis ,Protein Aggregation ,amyloid-beta ,Brain Disorders ,5.1 Pharmaceuticals ,Neurological ,alpha-Synuclein ,Dementia ,Development of treatments and therapeutic interventions - Abstract
Neurodegenerative diseases are characterized by the pathologic accumulation of aggregated proteins. Known as amyloid, these fibrillar aggregates include proteins such as tau and amyloid-β (Aβ) in Alzheimer’s disease (AD) and alpha-synuclein (αSyn) in Parkinson’s disease (PD). The development and spread of amyloid fibrils within the brain correlates with disease onset and progression, and inhibiting amyloid formation is a possible route toward therapeutic development. Recent advances have enabled the determination of amyloid fibril structures to atomic-level resolution, improving the possibility of structure-based inhibitor design. In this work, we use these amyloid structures to design inhibitors that bind to the ends of fibrils, “capping” them so as to prevent further growth. Using de novo protein design, we develop a library of miniprotein inhibitors of 35 to 48 residues that target the amyloid structures of tau, Aβ, and αSyn. Biophysical characterization of top in silico designed inhibitors shows they form stable folds, have no sequence similarity to naturally occurring proteins, and specifically prevent the aggregation of their targeted amyloid-prone proteins in vitro. The inhibitors also prevent the seeded aggregation and toxicity of fibrils in cells. In vivo evaluation reveals their ability to reduce aggregation and rescue motor deficits in Caenorhabditis elegans models of PD and AD.
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- 2022
39. Design, synthesis, biological evaluation and molecular docking study of novel urea-based benzamide derivatives as potent poly(ADP-ribose) polymerase-1 (PARP-1) inhibitors
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Guoqing Lu, Wenxing Nie, Meixiu Xin, Yingfen Meng, Jiayi Gu, Hui Miao, Xinyi Cheng, Albert S.C. Chan, and Yong Zou
- Subjects
Pharmacology ,Caspase 3 ,Organic Chemistry ,Poly (ADP-Ribose) Polymerase-1 ,Antineoplastic Agents ,General Medicine ,Poly(ADP-ribose) Polymerase Inhibitors ,Molecular Docking Simulation ,Structure-Activity Relationship ,Cell Line, Tumor ,Drug Discovery ,Benzamides ,Humans ,Urea ,Poly(ADP-ribose) Polymerases ,Cell Proliferation - Abstract
Poly(ADP-ribose) polymerase-1 (PARP-1) is one of the key members of DNA repair enzymes that is responsible for the repair of DNA single-strand breaks. Inhibition of PARP-1 has been demonstrated to be a promising strategy to selectively kill tumor cells by targeting DNA repair pathway. Herein, a series of novel urea-based benzamide derivatives were designed and synthesized based on the structure-based drug design strategy. The anticancer activities against five human cancer cell lines including HCT116, MDA-MB-231, HeLa, A579 and A375 were evaluated and the preliminary structure-activity relationships were summarized. Among them, compounds 23f and 27f exhibited potent antiproliferative effects against HCT116 cells with IC
- Published
- 2022
40. Discovery of novel benzamide derivatives bearing benzamidophenyl and phenylacetamidophenyl scaffolds as potential antitumor agents via targeting PARP-1
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Guoqing Lu, Wenxing Nie, Meixiu Xin, Yingfen Meng, Jiayao Jiang, Jiayi Gu, Xinyi Cheng, Albert S.C. Chan, and Yong Zou
- Subjects
Pharmacology ,Organic Chemistry ,Drug Discovery ,General Medicine - Published
- 2023
41. Engineering Gac/Rsm Signaling Cascade for Optogenetic Induction of the Pathogenicity Switch in Pseudomonas aeruginosa
- Author
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Shuai Yang, Xinyi Cheng, Lu Pu, Shengwei Fu, Xiaochen Xing, Lei Ni, Shuqiang Huang, Aiguo Xia, and Fan Jin
- Subjects
0106 biological sciences ,0303 health sciences ,Strain (chemistry) ,Pseudomonas aeruginosa ,Kinase ,Biomedical Engineering ,General Medicine ,Biology ,Optogenetics ,medicine.disease_cause ,Pathogenicity ,biology.organism_classification ,01 natural sciences ,Biochemistry, Genetics and Molecular Biology (miscellaneous) ,Small molecule ,Cell biology ,03 medical and health sciences ,010608 biotechnology ,medicine ,Signal transduction ,Caenorhabditis elegans ,030304 developmental biology - Abstract
Bacterial pathogens operate by tightly controlling the pathogenicity to facilitate invasion and survival in host. While small molecule inducers can be designed to modulate pathogenicity to perform studies of pathogen-host interaction, these approaches, due to the diffusion property of chemicals, may have unintended, or pleiotropic effects that can impose limitations on their use. By contrast, light provides superior spatial and temporal resolution. Here, using optogenetics we reengineered GacS of the opportunistic pathogen Pseudomonas aeruginosa, signal transduction protein of the global regulatory Gac/Rsm cascade which is of central importance for the regulation of infection factors. The resultant protein (termed YGS24) displayed significant light-dependent activity of GacS kinases in Pseudomonas aeruginosa. When introduced in the Caenorhabditis elegans host systems, YGS24 stimulated the pathogenicity of the Pseudomonas aeruginosa strain PAO1 in a brain-heart infusion and of another strain, PA14, in slow killing media progressively upon blue-light exposure. This optogenetic system provides an accessible way to spatiotemporally control bacterial pathogenicity in defined hosts, even specific tissues, to develop new pathogenesis systems, which may in turn expedite development of innovative therapeutics.
- Published
- 2021
42. Rhenium‐Catalyzed Arylation–Acyl Cyclization between Enol Lactones and Organomagnesium Halides: Facile Synthesis of Indenones
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Konstantin Karaghiosoff, Xingchen Liu, Jie Li, Ying Hu, Xinyi Cheng, and Binjing Hu
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Nucleophilic addition ,010405 organic chemistry ,chemistry.chemical_element ,Regioselectivity ,Halide ,General Medicine ,General Chemistry ,Rhenium ,Bond formation ,010402 general chemistry ,01 natural sciences ,Medicinal chemistry ,Enol ,Catalysis ,0104 chemical sciences ,chemistry.chemical_compound ,chemistry ,Intramolecular force - Abstract
A set of rhenium-catalyzed arylation-acyl cyclizations between (hetero)arylmagnesium halides and enol lactones through a cascade C(sp2 )-C(sp2 )/C(sp2 )-C(sp2 ) bond formation under mild reaction conditions has been developed. Indeed, a wide range of functional groups on both organomagnesium halides and enol lactones is well tolerated by the simple rhenium catalysis, thus furnishing polyfunctionalized indenones in one-pot fashion and with complete control of the regioselectivity. Moreover, this approach also provides a straightforward synthetic route to neolignan and (iso)pauciflorol F. Mechanistic studies demonstrated that the reaction involves a sequence of syn-carborhenation and intramolecular nucleophilic addition.
- Published
- 2021
43. Molecular cloning, characterization, and expression analysis of TIPE1 in chicken (Gallus gallus): Its applications in fatty liver hemorrhagic syndrome
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Xinyi Cheng, Jiuyue Liu, Yibo Zhu, Xiaoquan Guo, Ping Liu, Caiying Zhang, Huabin Cao, Chenghong Xing, Yu Zhuang, and Guoliang Hu
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Heart Septal Defects, Ventricular ,Mammals ,Hemorrhage ,General Medicine ,Syndrome ,Biochemistry ,Antibodies ,Craniofacial Abnormalities ,Fatty Liver ,Liver ,Structural Biology ,Animals ,Abnormalities, Multiple ,Female ,Cloning, Molecular ,Molecular Biology ,Chickens ,Growth Disorders ,Poultry Diseases - Abstract
Tumor necrosis factor-α-induced protein eight like 1 (TIPE1) plays important role in autophagy, immunity, and lipid metabolism. The potential role of TIPE1 in fatty liver hemorrhage syndrome (FLHS) is elusory. In the present study, the full-length coding sequence of TIPE1 was cloned, and the polyclonal antibody of TIPE1 was produced by the recombinant TIPE1 protein. The bioinformatic analysis showed that the chicken TIPE1 protein, which was predicted to be a hydrophobic and non-transmembrane protein without signal peptide was highly different from that of mammals. Furthermore, proceeded by using TIPE1 polyclonal antibody, the tissue distribution analysis showed that TIPE1 protein is ubiquitously expressed in various tissues in adult hens and chicks, with its level being higher in the liver and, spleen, moderate in intestinal, brain, and heart. Besides, immunohistochemistry and immunofluorescence observation demonstrated that TIPE1 mainly existed in the cytoplasm in liver, duodenum, and cecum cell. Notably, the TIPE1 expressions were significantly decreased in laying hens suffering from FLHS. Collectively, these results showed that the chicken TIPE1 polyclonal antibody was successfully prepared and further used to analyze the expression profiles of chicken. And the expression of TIPE1 was reduced in FLHS which provided the foundation for further investigation in FLHS.
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- 2022
44. The Causes of Social Anxiety Disorder in the Different Developmental Stages
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Yuwen Yang and Xinyi Cheng
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- 2022
45. Baicalin ameliorates APEC-induced intestinal injury in chicks by inhibiting the PI3K/AKT-mediated NF-κB signaling pathway
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Fan Yang, Xinyi Cheng, Zhanyou Cao, Huabin Cao, Yu Zhuang, Chenghong Xing, Ruiming Hu, Xiaoquan Guo, Guoliang Hu, and Junrong Luo
- Subjects
animal structures ,avian pathogenic Escherichia coli ,intestinal injury ,Occludin ,SF1-1100 ,Proinflammatory cytokine ,Superoxide dismutase ,Phosphatidylinositol 3-Kinases ,IMMUNOLOGY, HEALTH AND DISEASE ,Escherichia coli ,Animals ,Baicalin ,Protein kinase B ,PI3K/AKT/mTOR pathway ,Escherichia coli Infections ,chemistry.chemical_classification ,Flavonoids ,biology ,Kinase ,Glutathione peroxidase ,PI3K/AKT/NF-κB, chick ,NF-kappa B ,General Medicine ,Molecular biology ,Animal culture ,chemistry ,biology.protein ,Animal Science and Zoology ,Tumor necrosis factor alpha ,Chickens ,Proto-Oncogene Proteins c-akt ,Signal Transduction - Abstract
Avian pathogenic Escherichia coli (APEC) is the causative agent of avian colibacillosis. Baicalin (BA) possesses multiple pharmacological effects, but the mechanism underlying its activity in APEC-induced intestinal injury remains unknown. This study aims to investigate the protective effects and possible mechanism of BA against APEC-induced intestinal injury. Sixty 1-day-old chicks were randomly divided into 4 groups: the control group (basal diet), E. coli group (basal diet), BAI10 group (10 mg/kg BA), and BAI20 group (20 mg/kg BA). After pretreatment with BA for 15 d and subsequent induction of APEC infection by pectoralis injection, the ileum was collected and analyzed. The results showed that BA-pretreatment demonstrated an alleviation of chicks in diarrhea rate, mortality, and histopathological changes in intestinal tissues after APEC infection. Additionally, following APEC infection, BA improved the intestinal barrier by elevating zona occludens (ZO)s (ZO-1, 2, 3), Claudins (Claudin1, 2, 3), Occludin, avian β-defensin (AvBD)s (AvBD1, 2, 4), lysozyme (Lyz) mRNA levels and ZO-1, Claudin1, and Occludin protein levels. Besides, the activities of total superoxide dismutase (T-SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) and the SOD-1 and CAT mRNA levels and SOD-1 protein level were elevated by BA pretreatment. BA pretreatment also decreased the malondialdehyde (MDA) content, heme oxygenase-1 (HO-1) and NADH quinone oxidoreductase 1 (NQO1) mRNA levels, and HO-1 protein level after APEC infection. BA alleviated the APEC-induced inflammatory response, including downregulating the mRNA levels of proinflammatory cytokines (tumor necrosis factor-α (TNF-α), interleukin [IL]-1β, IL-6, IL-8) and upregulating the mRNA levels of anti-inflammatory cytokines (IL-4, IL-10, IL-13, transforming growth factor-β [TGF-β]). Furthermore, BA decreased the mRNA and protein levels of phosphatidylinositol 3 kinase (PI3K), protein kinase B (AKT), and nuclear factor kappa-B (NF-κB) as well as the expression of the phosphorylated forms of these proteins after APEC infection. Collectively, our findings indicate that BA exerts a protective effect against APEC-induced intestinal injury in chicks by inhibiting the PI3K/AKT-mediated NF-κB pathway, suggesting that BA may be a potential therapeutic approach for avian colibacillosis.
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- 2022
46. Research on Nobel Prize Winning in Japan and the Construction of Practical and Innovative Student Teams in Private Colleges
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Changping, Zhu, primary, Yinbing, Peng, additional, Mengqiu, Sun, additional, Xingxing, Tong, additional, Xinyi, Cheng, additional, Wanwan, Li, additional, and Wenjing, Wang, additional
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- 2022
- Full Text
- View/download PDF
47. 17‐3: A Novel Pixel‐level Local Dimming Backlight System for HDR Display Based on mini‐LED
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Xinyi Cheng, Li Liang, Xitong Ma, Enhui Guan, Wang Zhimao, Xiao Zhang, Ran Duan, Shuo Chen, Li Xianzhen, and Mu Xinxin
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Pixel ,Computer science ,business.industry ,Organic Chemistry ,Computer vision ,Artificial intelligence ,Backlight ,business ,Biochemistry - Published
- 2020
48. Pseudo-Noise Code Shifting Signal for AI Arranged UAV Networking
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Jing Zhang, Deyue Zou, Jie Liu, Yunfeng Liu, Shouchuan Ma, and Xinyi Cheng
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Computer Networks and Communications ,business.industry ,Code division multiple access ,Noise (signal processing) ,Computer science ,Process gain ,ComputerApplications_COMPUTERSINOTHERSYSTEMS ,020206 networking & telecommunications ,02 engineering and technology ,Transmission (telecommunications) ,Hardware and Architecture ,Pseudorandom noise ,Modulation ,0202 electrical engineering, electronic engineering, information engineering ,Key (cryptography) ,Code (cryptography) ,020201 artificial intelligence & image processing ,business ,Software ,Computer hardware ,Information Systems - Abstract
Communication problems standout as the key issue needing to be addressed in Unmanned Aerial Vehicle (UAV) applications. Nowadays, the application of Artificial Intelligence (AI) technology provides a more flexible and effective organizing strategy for the UAV formation, but it also brings the challenges of transmission speed and access speed for the UAV networking technology.This highlights the importance of multi-access technology in UAV communication. Code Division Multiple Access (CDMA) is a suitable multi-access technology for UAV networking, but low spectrum utilization limits its application. In this study, we use a Pseudo-Noise (PN) code shifting modulation method to improve the spectrum utilization of CDMA signals, which makes it more suitable for UAV communication applications. Theoretical analysis and simulations show that the PN code shifting modulation strategy can effectively improve the information transmission rate of the system without affecting the processing gain and its multi-access capability.
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- 2020
49. Multiple approaches for massively parallel sequencing of SARS-CoV-2 genomes directly from clinical samples
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Jielun Cai, Yanping Gong, Taiqing Feng, Chen Tian, Xiaoqing Liu, Huanming Yang, Huahui Ren, Wenchen Song, Jincun Zhao, Xun Xu, Minfeng Xiao, Huanzi Zhong, Yanyan Zhang, Jian Wang, Shida Zhu, Yanqun Wang, Lin Yang, Ziqing Deng, Yang Guifang, Tianzhu Liang, Jiandong Li, Daxi Wang, Peidi Ren, Xinyi Cheng, Yanping Zhao, Fang Chen, Junhua Li, Zhihua Ou, Jingkai Ji, Yimin Li, Honglong Wu, Min Li, Wanying Sun, and Weijun Chen
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0301 basic medicine ,Emerging infectious diseases ,Metatranscriptomic sequencing ,lcsh:QH426-470 ,viruses ,030106 microbiology ,Pneumonia, Viral ,lcsh:Medicine ,Viral quasispecies ,Computational biology ,Genome, Viral ,Biology ,Genome ,DNA sequencing ,03 medical and health sciences ,Betacoronavirus ,Genomic surveillance ,Multiplex polymerase chain reaction ,Genetics ,Humans ,iSNV ,Molecular Biology ,Pandemics ,Genetics (clinical) ,Whole genome sequencing ,Massive parallel sequencing ,Hybrid capture ,Whole Genome Sequencing ,SARS-CoV-2 ,Research ,lcsh:R ,Genetic Variation ,High-Throughput Nucleotide Sequencing ,COVID-19 ,Amplicon ,Multiplex PCR ,Virus evolution ,Quasispecies ,lcsh:Genetics ,030104 developmental biology ,Viral evolution ,Host-Pathogen Interactions ,Molecular Medicine ,RNA, Viral ,Coronavirus Infections ,Multiplex Polymerase Chain Reaction - Abstract
Background COVID-19 (coronavirus disease 2019) has caused a major epidemic worldwide; however, much is yet to be known about the epidemiology and evolution of the virus partly due to the scarcity of full-length SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) genomes reported. One reason is that the challenges underneath sequencing SARS-CoV-2 directly from clinical samples have not been completely tackled, i.e., sequencing samples with low viral load often results in insufficient viral reads for analyses. Methods We applied a novel multiplex PCR amplicon (amplicon)-based and hybrid capture (capture)-based sequencing, as well as ultra-high-throughput metatranscriptomic (meta) sequencing in retrieving complete genomes, inter-individual and intra-individual variations of SARS-CoV-2 from serials dilutions of a cultured isolate, and eight clinical samples covering a range of sample types and viral loads. We also examined and compared the sensitivity, accuracy, and other characteristics of these approaches in a comprehensive manner. Results We demonstrated that both amplicon and capture methods efficiently enriched SARS-CoV-2 content from clinical samples, while the enrichment efficiency of amplicon outran that of capture in more challenging samples. We found that capture was not as accurate as meta and amplicon in identifying between-sample variations, whereas amplicon method was not as accurate as the other two in investigating within-sample variations, suggesting amplicon sequencing was not suitable for studying virus-host interactions and viral transmission that heavily rely on intra-host dynamics. We illustrated that meta uncovered rich genetic information in the clinical samples besides SARS-CoV-2, providing references for clinical diagnostics and therapeutics. Taken all factors above and cost-effectiveness into consideration, we proposed guidance for how to choose sequencing strategy for SARS-CoV-2 under different situations. Conclusions This is, to the best of our knowledge, the first work systematically investigating inter- and intra-individual variations of SARS-CoV-2 using amplicon- and capture-based whole-genome sequencing, as well as the first comparative study among multiple approaches. Our work offers practical solutions for genome sequencing and analyses of SARS-CoV-2 and other emerging viruses.
- Published
- 2020
50. Novel Online PET Imaging for Intrabeam Range Verification and Delivery Optimization: A Simulation Feasibility Study
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Weiguo Lu, Zhenyu Xiong, Kun Hu, Mingli Chen, Yuncheng Zhong, Yiping Shao, and Xinyi Cheng
- Subjects
Range (particle radiation) ,Accuracy and precision ,Materials science ,Particle therapy ,medicine.diagnostic_test ,business.industry ,medicine.medical_treatment ,Article ,Atomic and Molecular Physics, and Optics ,Imaging phantom ,Positron ,Optics ,Positron emission tomography ,medicine ,Radiology, Nuclear Medicine and imaging ,Particle beam ,business ,Instrumentation ,Beam (structure) - Abstract
Online positron emission tomography (PET) image-based method uses an initial particle beam to measure the particle beam range (BR) within the same fraction so that any measured range-shift with respect to the predicted BR can be compensated before the rest therapeutic beam deliveries. However, the method requires to use a low-dose initial beam to minimize the risk of beam overshooting, which leads to low image count and inaccurate BR measurement. In this in-silico study, we evaluate the feasibility of a new online PET imaging method that measures BR at the mid-plane of a target volume with part of the high-dose therapy beams to verify BR and guide adaptive treatment replanning. Simulations included various processes of proton beam radiations to a tumor inside a human–brain phantom, positron, and PET image generation at the mid-plane with initial beams, activity range measurement, and range-shift compensated beam delivery. The results demonstrated that the new method, under the simulated conditions, can achieve ~1.1-mm mid-plane BR measurement accuracy and closely match the delivered range-shift compensated dose distribution with the planned one. Overall, it is promising that this new method may significantly improve the particle therapy accuracy.
- Published
- 2020
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